title: Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on silk-hydroxyapatite films.
abstract: The goal of this study was to explore the effects of osteoporosis-related therapeutics on bone remodeling in vitro. A previously established bone-tissue mimetic system consisting of silk protein biomaterials in combination with hydroxyapatite and human cells was used for the study. Silk-hydroxyapatite films were pre-complexed with the non-nitrogenous bisphosphonate clodronate or the nitrogenous bisphosphonate alendronate and cultured with THP-1 human acute monocytic leukemia cell line-derived osteoclasts, human mesenchymal stem cell derived osteoblasts or a direct co-culture of the two cell types. Metabolic activity, calcium deposition and alkaline phosphatase activity were assessed over 12 weeks, and reconstructed remodeled biomaterial surfaces were also evaluated for quantitative morphological changes. Increased metabolic activity and increased roughness were found on the clodronate-complexed biomaterial substrates remodeled by osteoblasts and co-cultures of osteoblasts with osteoclasts, even at doses high enough to cause a 90% decrease in osteoclast metabolic activity. Films complexed with low doses of alendronate resulted in increased metabolic activity and calcium deposition by osteoblasts, while higher doses were similarly toxic among osteoclasts, osteoblasts and co-cultures. These results point to the utility of these well-defined bone-mimetic in vitro cultures as useful screens for therapeutics for bone-related diseases, particularly with the ability to conduct studies for extended duration (here for 12 weeks) and with pre-complexed drugs to mimic conditions found in vivo.
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA 02155, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Hayden
authors.forename: Moritz
authors.initials: M
authors.lastname: Vollrath
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D012831:Bombyx; D002118:Calcium / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology*; D018920:Coculture Techniques; D004164:Diphosphonates / Q000494:pharmacology; D017886:Durapatite / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047011:Silk / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D004164:Diphosphonates; D047011:Silk; D004002:Clodronic Acid; D017886:Durapatite; D002118:Calcium; D019386:Alendronate
keywords: Bisphosphonates; Co-culture; Osteoporosis; Silk